title: Insulin degludec: a long-acting modern insulin analogue with a predictable pharmacokinetic/pharmacodynamic profile.
abstract: Insulin degludec is, like insulin detemir, a product of coupling of Des-B30 threonine insulin to fatty acid side chains. After injection, degludec self associates, precipitating in subcutaneous tissue. There is a continuous and highly predictable slow dissociation of insulin monomers from this depot; insulin levels rise immediately reaching tmax at 10-12 hours, followed by a slow decline with a t½ of 17-21 hours, roughly double the duration of action of insulin glargine. An important property of degludec not shared by glargine is miscibility with rapid-acting insulin. Although the effect of coadministered insulin aspart is somewhat blunted by coformulation with degludec, a preparation of 70% degludec and 30% aspart has predictable pharmacodynamics. Daily administration of degludec has glucose-lowering benefits not different from those of glargine, with purportedly less hypoglycemia. Although degludec is approved and marketed in Europe under the brand name Tresiba®, the U.S. Food and Drug Administration, in a surprising development, challenged the assertion of lower tendency to hypoglycemia with degludec, and, more importantly, raised concerns that degludec may have a higher cardiovascular risk than glargine. Only a long-term study in a large patient population can resolve these questions. However, release of degludec for marketing to appropriate patients should proceed while awaiting the results of such a study.
authors.affiliation: Creighton University, School of Medicine, and Association of Diabetes Investigators, Creighton Diabetes Center, Omaha, Nebraska, USA. Rendell@asndi.com
authors.forename: M
authors.initials: M
authors.lastname: Rendell
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy*; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec
keywords: Diabetes type 1; Diabetes type 2; Insulin analogue; Insulin degludec; NN-1250